Glaucoma is a leading cause of blindness. Diagnosis and monitoring of glaucoma is of particular importance because the onset is insidious and the visual damage is irreversible. The goal of the Advanced Imaging for Glaucoma (AIG) study (www.AIGStudy.net) is to improve early detection and long-term monitoring of glaucoma by advancing the technology of optical coherence tomography (OCT), which is uniquely capable of imaging eye structures affected by glaucoma with micrometer precision. In AIG Phase I, very high-speed Fourier-domain (FD) OCT achieved higher diagnostic accuracy than other quantitative imaging technologies. Significantly, glaucoma diagnosis was made using OCT maps of macular ganglion cells and measurement of retinal blood flow. In the proposed Phase II, the next generation OCT hardware and analytic software will be developed. A longitudinal clinical study will demonstrate advantages in the early detection and prediction of disease progression. The specific aims are: 1. Develop image processing and diagnostic analysis for 3-dimensional (3D) OCT data. We will improve 3D image processing software to detect the loss of ganglion cells, nerve fibers, optic disc rim, and track glaucoma progression. 2. Develop ultrafast OCT systems for imaging the macula and optic nerve head. We will develop the next generation technology that is up to 40 times faster (1 MHz) than current FD-OCT. It will be capable of capturing full tissue volume in 0.1-0.2 second to achieve 3D sampling without significant motion error. 3. Develop Doppler OCT to measure retinal perfusion. Retinal blood flow measurement with Doppler OCT correlates very well with glaucoma status. This ground-breaking advance in functional imaging will be made practical with higher speed and automated software. 4. Evaluate OCT technologies in a longitudinal clinical study. An extension of the ongoing clinical study is proposed. Participants (665 including 400+ already enrolled) in normal, glaucoma suspect, and glaucoma groups will be followed. OCT and other imaging technologies will be compared for diagnostic accuracy, detection of early progression, and prediction of future visual field loss. The impact of intraocular pressure on retinal blood flow and how flow affects the risk of glaucoma will also be studied. Quantitative imaging technologies such as OCT have improved glaucoma management by reducing reliance on insensitive tests such as perimetry and subjective disc grading. The AIG Partnership comprises engineers and clinicians who co-invented OCT. We propose to further improve its performance with higher speed, more sophisticated software, and novel functional measurements. The eventual goal is to save vision by basing glaucoma treatment decisions on speedy and reliable imaging tests. PUBLIC HEALTH RELEVANCE: Glaucoma is a chronic and irreversible degeneration of the retina and optic nerve that is often caught only in the later stages by current standard tests such as visual field and clinical optic disc evaluation. This project aims to improve the detection of glaucoma and the measurement of its progression using optical coherence tomography (OCT), the only imaging technology that can measure retinal degeneration with microscopic resolution. Accurate monitoring of glaucoma with OCT will improve treatment decisions regarding surgery or eye drops, both of which are effective but also carry significant side effects and risks.